The aim of this project is the study of the Fv-1 gene mediated host control of murine retroviruses. Results recently have shown that N-tropic MuLV which had been rendered non-infectious by physical agents (gamma irradiation, heat) is able to abrogate Fv-1 restriction in Balb/3T3 cells, thus indicating that abrogation of cellular restriction and viral infectivity are two different phenomena. These results confirmed our previous findings using N-tropic MSV pseudotypes. We presently use heat-inactivated MuLV stocks, with very low infectivity and high abrogating activity, for the study of another type of murine leukemia virus, the amphotropic virus, which possesses the ability of replicating in cells of a variety of mammalian species. Preliminary results have shown that amphotropic MuLV has a host range in mouse cells apparently identical to that of N-tropic MuLV. Also, amphotropic MuLV is able to abrogate Fv-1b restriction in Balb/3T3 cells, rendering them permissive to infection with either N-tropic ecotropic MuLV or additional amphotropic MuLV. Similarly, N-tropic ecotropic MuLV can render Balb/3T3 cells permissive to subsequent infection with amphotropic MuLV. Also in progress are studies on the mechanisms of Fv-1 restriction and its abrogation in NXBF1 dually restrictive hybrid cells.